The goal of the Cancer Imaging and Radiobiology Research Program (CIR) is to stimulate and promote investigations to develop and evaluate new cancer diagnostic and treatment strategies that utilize biophysics and engineering to improve imaging technology and to understand biological and physiological factors that influence the effectiveness of radiotherapy and other forms of treatment. CIR provides a forum for discussion and advancement of (a) novel preclinical and clinical imaging methods and modalities; (b) tools and techniques for in vivo oxygen assessment; (c) nanotechnology-mediated therapy and imaging; and (d) translation of these approaches into diagnostic and therapeutic clinical trials. The CIR has 19 members from six departments with $7.9 million in peer-reviewed funding (total costs, with $4.6 million from NCI, 58%) that includes awards in the P-series (P01, P41) and U-series (U54) funding mechanisms. The publication record over the past five years exceeds 230 papers of which approximately 58% involve intra-program collaborations and 18% represent inter-program collaborations. These data represent evidence of a highly productive and interactive research program. CIR research activities during the current funding period have led to the first technical reports and initial clinical evaluations of several innovative instrumentation platforms, including MR-guided NIR (near infrared) spectral imaging; microwave mammography; and clinical EPR oximetry. These and other cutting-edge developments involving electrical impedance spectroscopy, magnetic resonance elastography, fluorescence-guided resection, magnetic resonance microwave absorption imaging, nanoparticle hyperthermia, and magnetic nanoparticle imaging, among others, target cancers of breast, brain, head and neck, and prostate. These are tumor sites for which active diagnostic and therapeutic clinical studies are underway at NCCC. Research within the CIR currently focuses on (1) imaging structural and functional parameters associated with malignancy for detection, characterization, and therapyguidance of the disease; (2) measurement and assessment of oxygen during cancer treatment; and (3) delivery and assessment of agents and doses for evaluating new cancer imaging modalities, therapeutics and exposure outcomes. The range of physical techniques under investigation by the CIR membership provides a novel framework, enabled through NCCC support, for combining both conceptually and practically new approaches for clinical decision-making in the identification and management of cancer patients.